A biochip is a biosensor technology in which several tens to several tens of thousands different analysis substances are fixed onto a solid surface, and a specific signal is analyzed by using an analysis equipment to be utilized in a wide range of fields such as a biolabeling substance screening, a disease diagnosis, an environment monitoring, and the like. Examples of a substrate used in a biochip include a silicone wafer, a hydrogel (PerkinElmer Life sci), a hybond ECL membrane (Anal. Biochem, 294, 55, 2001), a glass surface, a thin-film NC slide (J. Biomol. Technol, 18, 245, 2007), a photonic crystal surface, an NC slide, and the like, and a method of fixing a target substance onto a surface by using an adsorption method and a covalently bonding method has been known.
The biochip is measured by fixing different biosubstances onto a surface of a sensor into which a reactor capable of fixing the biosubstances is introduced, and reacting the biosubstances with an analysis substance to react a secondary reaction substance having a labeled specific substance, and using an analysis equipment. As a method of manufacturing a multiple analysis of biochip, methods such as a microarray, a light patterning, and the like, have been used. As the labeling substance, various labeling substances in addition to enzymes, luminescences, fluorescent nanoparticles, metal nanoparticles, and quantum dot have been used. In addition, various kinds of measuring systems such as a fluorescent scanner, a SPR biosensor, a light absorption sensor, and the like, depending on a labeling shape and the surface have been involved.
The biochip which is the most widely used for disease diagnosis, new medicine development, or the like, is a diagnosis sensor fixing antibody or antigen protein onto the surface of the sensor to screen a candidate substance or to diagnose the occurrence of a specific disease in a patient sample. However, a detection sensitivity of the biochip researched up to now is several pg/ml to several tens of pg/ml, and thus, it is not possible to analyze a biomarker having a concentration of a pg/ml unit or less in a human body. As an example, in the case of cytokine intermediating signal transmission between cells among important biomarkers present in the human body, most of cytokine is present at a concentration of a pg/ml unit or less, such that it is almost impossible to analyze the cytokine by using biochip technologies. In addition, since most of the existing analysis equipments analyzing the biochips, such as a fluorescent scanner, a SPR sensor, and the like, are slightly expensive, economic feasibility of the measuring equipments is an important problem to be solved. Therefore, in order to implement development of more advanced biomarkers, screening of new medicine candidate substances, disease diagnosis, and the like, through the biochip technology, development of a new biochip technology capable of having economic feasibility and achieving high sensitivity measurement as compared to the existing technologies is urgently needed.
In order to improve the detection sensitivity of the biochip, a method of improving the detection sensitivity of a label system to be used and an effective signal analysis system are required. A chemiluminescence method has been known as an ultra high sensitivity detection method showing detection sensitivity of a zeptomole (10−18 to 10−21 mole) level in an immune reaction (Clin Biochem, 26, 325, 1993). Recently, an example of applying the chemiluminescence method to a diagnostic sensor such as a high sensitivity strip sensor has been gradually increased (BioChip J. 4(2), 155, 2010).
A number of patents such as U.S. Pat. No. 8,021,848, U.S. Patent Application Publication No. 2005/0190286 reported a number of sensors such as bioimaging using a CMOS image sensor, a fluorescent sensor, a magnetic sensor, and the like.
However, development of the biosensor having excellent detection sensitivity and improved light sensitivity of the sensor as compared to the measurement method has been continuously required.